Researchers Map Human Genome in 4-D as it Folds

Source: Baylor College of Medicine

Summary: A multi-institutional team of researchers for the first time created a high-resolution 4-D map of an entire human genome as it folds over time.

For decades, it was suspected that in response to stimulus DNA elements in a human cell which lie far apart in the human genome find one another and form loops along the chromosome. In 2014 it was possible to map these loops but the loops were static and it was not possible to watch the loops change. A multi-institutional team of researchers from Baylor College of Medicine, Rice University, Stanford University and the Broad Institute of MIT and Harvard for the first time created a high-resolution 4-D map of an entire human genome as it folds over time. The report was published in the journal Cell.

DNA loops are formed in the presence of cohesin


The folding process over time of the genome was tracked by disrupting a ring-shaped protein complex called cohesin which was located at the boundaries of loops. DNA loops are created by cohesin through a process called extrusion. Everything has not happened as the researchers expected. Some odd loops were observed which did exactly opposite of what they were anticipated to do. It was realized that apart from extrusion, a second mechanism, compartmentalization (cohesin was not involved) is observed. Both mechanisms are involved in bringing DNA elements together but they operate quite differently. This discovery may lead to new ways of understanding genetic diseases.

Suhas S.P. Rao, first author of the study said, “Before, we could make maps of how the genome folded when it was in a particular state, but the problem with a static picture is that if nothing ever changes, it’s hard to figure out how things work, Our current approach is more like making a movie; we can watch folds as they disappear and reappear.”

Eric Lander, co-author said, “We’re beginning to understand the rules by which DNA elements come together in the nucleus. Now that we can track the elements as they move over time, the underlying mechanisms are starting to become clearer.”

More Information: Suhas S.P. Rao et al, “Cohesin Loss Eliminates All Loop Domains”, Cell (2017).

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